We have cloned several members of the Class II a-mannosidases including two glycoprotein processing enzymes, termed a-mannosidases II and IIx, and two a-mannosidases involved in glycoprotein catabolism. We are presently characterizing the roles of the processing a-mannosidases in the maturation of mammalian glycoproteins by generating expression constructs for detailed substrate specificity studies and generating mouse knockouts for the processing mannosidases (in collaboration with Dr. Jamie Marth in an associated project). In addition, the human genetic disease characterized by an enzymatic defect in a-mannosidase II (HEMPAS disease) is being elucidated by determining its molecular basis as well as by generating a mouse model for the human genetic deficiency.